Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DBP”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2002

Purging effect of dibutyl phthalate on leukemia cells involves fas independent activation of caspase-3/CPP32 protease.

We previously found that dibutyl phthalate (DBP) had a pharmacological activity in eliminating tumor cells and could be used as a purging agent in autologous bone marrow transplantation. In this study, we show that DBP can induce apoptosis in MO7e and U937 leukemia cell lines. Treatment of these cells with DBP up-regulates cellular activity of caspase-3/CPP32 and causes apoptosis rapidly as determined by cell viability and dUTP nick end labeling assay. Activation of caspase-3/CPP32 and cleavage of poly(ADP-ribose) polymerase were determined in DBP-induced apoptosis of leukemia cells. However, DBP treatment did not induce the expression of fas. Two caspase inhibitors, z-VAD-fmk and N-acetyl-Asp-Glu-Val-Asp-aldehyde partly blocked the cell death of MO7e cells induced by DBP. These results suggest that fas-independent activation of caspase-3 protease plays important roles in the purging effect of DBP on leukemia cells.

Amino Acid Chloromethyl Ketones↗
PubMed2002

Comparison of embryotoxicity of ESBO and phthalate esters using an in vitro battery system.

Epoxidized soy bean oil (ESBO) and phthalate esters have been used as a plasticizer in polyvinyl chloride products. In this study, the embryotoxicity of ESBO and phthalate esters, namely, diethyl hexyl phthalate (DEHP), butylbenzyl phthalate (BBP) and dibutyl phthalate (DBP) was evaluated using short-term in vitro battery system, such as the whole embryo, midbrain and limb bud culture systems. Whole embryos at gestation day 9.5 were cultured for 48 h and the morphological scoring was measured. The cytotoxic effect and differentiation for mid-brain (MB) and limb bud (LB) cell were assessed by 50% inhibition concentration (IC(50)) with neutral red uptake and hematoxylin-stained foci (MB) or Alcian Blue staining (LB), respectively. In the whole embryo culture assay, ESBO (83, 250 and 750 microg/ml) exerted no toxic effect on growth and development of the embryo, whereas phthalate esters (1, 10, 100 microg/ml for DEHP, 10, 100, 1,000 microg/ml for BBP and DBP) inhibited growth and development dose dependently. In mid-brain and limb bud culture, the IC(50) of differentiation and cytotoxicity in BBP was 412.24 and 231. 76 microg/ml for mid-brain, and 40.13 and 182.38 microg/ml for limb bud, respectively. The IC(50) of differentiation and cytotoxicity in DBP was 27.47 and 44.53 microg/ml for mid-brain, and 21.21 and 25.54 microg/ml for limb bud cells, respectively. The lower IC(50) in both cells was obtained from DBP when compared to BBP. From these results, limb bud cells responded more sensitively to BBP and DBP than mid-brain cells. The IC(50) of limb bud cell differentiation and cytotoxicity in DBP is 1.9 and 7.1 less than that of BBP. However, any alteration in cytotoxicity and differentiation was observed with ESBO treatment. These studies suggested that ESBO is not embryotoxic; however, DEHP, BBP and DBP exhibit embryotoxic potential at high concentration.

Animals↗
PubMed1998

Effect of cancer chemopreventive agents on microsome-mediated DNA adduction of the breast carcinogen dibenzo[a,l]pyrene.

Due to the large and expanding number of potential cancer chemopreventive agents, there is an increasing need for short term tests to study the efficacy and mechanisms of these agents. In this study, we have employed a microsome-mediated test system to study the effect of several suspected chemopreventive agents on the DNA adduct formation capacity of the potent mammary carcinogen, dibenzo[a,l]pyrene (DBP). Bioactivation of DBP by Aroclor 1254-induced rat liver microsomes in the presence of calf thymus DNA (300 microg/ml) resulted in the formation of one major and six other prominent DNA adducts (324 adducts/10(7) nucleotides). These adducts were previously determined to be deoxyadenosine (dA) and deoxyanosine (dG)-derivatives of both anti- and syn-DBP-11,12-diol-13,14-epoxides (DBPDE). Intervention with ellagic acid, chlorophyllin, benzyl isocyanate (BIC), oltipraz or genistein (150 microM) strongly diminished DBP-DNA adduction by > or = 75%. Linoleic acid, curcumin and butylated hydroxytoluene (BHT) also significantly inhibited DBP DNA adduction (26-46%) while N-acetylcysteine (NAC) had no effect. Moreover, nonenzymatic studies with anti- and syn-DBPDE isomers revealed that chlorophyllin, ellagic acid, BIC and BHT may be inhibiting DBP-DNA adduction in an enzymatic-independent manner since these agents diminished DBPDE-DNA adduction by 30-75%. Genistein, oltipraz and curcumin did not diminish DBPDE-DNA adduction and therefore most likely require the presence of the microsomal subcellular fraction to inhibit DBP-DNA adduction.

Animals↗
PubMed1999

Neoplastic potential of rat tracheal epithelial cell lines induced by 1-nitropyrene and dibenzo(a,i)pyrene.

Our previous study showed that both 1-nitropyrene (1-NP) and dibenzo(a,i)pyrene (DBP) induced enhanced growth variants (EGVs) in primary cultures of rat tracheal epithelial (RTE) cells exposed in vivo. Cell lines were established from some of the EGVs. Further studies, using anchorage-independent growth in soft agar and tumorigenicity in athymic nude mice, were performed to determine the neoplastic potential of EGVs induced by 1-NP and DBP. Results show that three of five from DBP- and five of five from 1-NP-induced cell lines displayed anchorage-independent growth. The colony forming efficiency (CFE) from DBP-induced cell lines was 0.067 per thousand and CFE from 1-NP-induced cell lines was 0.151 per thousand. There is a significant difference between the two CFEs (mu = 12.08, P<0. 01). Two of five DBP- and five of five 1-NP-induced cell lines produced squamous cell carcinomas (SCC) in nude mice. The rate of tumorigenicity counted by injected sites was 20% (6/30) for DBP-induced cell lines and 57% (17/30) for 1-NP-induced cell lines. There is a significant difference between the results of tumorigenicity from the cell lines induced by the two different compounds (chi(2)=8.53, P<0.01). Neither of the two cell lines from spontaneously developed foci grew in soft agar or produced SCC in nude mice. It seems that the neoplastic potential of transformed RTE cells induced by 1-NP was higher than that of DBP.

Animals↗
PubMed1984

Brevin and vitamin D binding protein: comparison of the effects of two serum proteins on actin assembly and disassembly.

Actin depolymerizing activity in serum can be attributed to the two proteins brevin and vitamin D binding protein (DBP). To investigate their mechanisms of action, we used a number of techniques, including procedures involving the fluorescent pyrene-labeled actin probe, to compare the interaction of the two proteins with G- and F-actin in vitro. With a fluorescence enhancement assay, we determined that brevin forms a 1:2 complex and DBP forms a 1:1 complex with pyrene-G-actin. We also found that both proteins reduce the viscosity of F-actin measured with high-shear and low-shear viscometers, with brevin effective at much lower concentrations than DBP. In polymerization experiments, brevin inhibits filament elongation at substoichiometric levels by inhibiting monomer addition at the barbed end but can also accelerate polymerization by nucleating assembly of filaments which grow from the pointed end. DBP does not nucleate filament assembly and inhibits filament elongation at either end only at near-stoichiometric levels. Brevin, but not DBP, accelerates disassembly of filaments diluted into a depolymerizing medium. This is consistent with the capability of brevin to sever preformed filaments associated with erythrocyte membranes and to increase the number of filament ends as estimated by a cytochalasin binding assay. In steady-state experiments involving the use of pyrene-actin, brevin produces only a small increase in the apparent monomer concentration when the critical concentrations at the two ends of the filaments are the same (i.e., in 0.1 M KCl). However, when the critical concentration at the pointed end is higher than that at the barbed end (i.e., in 2 mM MgCl2), low molar ratios of brevin sharply increase the monomer concentration to the critical concentration of the pointed end. This allows substoichiometric amounts of brevin to completely depolymerize filaments when the total actin concentration is at or below that of the pointed end. In contrast to brevin, DBP increases the amount of nonfilamentous actin in a stoichiometric and dose-dependent manner regardless of the nature of the salt in the medium. We conclude from this study that brevin is similar in its mechanism of action to other proteins known to bind to the barbed end of filaments and that DBP is related in its action to proteins that complex monomers and prevent them from participating in the polymerization process.

Actins↗
PubMed2002

Crystal structure of the complex between actin and human vitamin D-binding protein at 2.5 A resolution.

A high-affinity complex formed between G-actin and plasma vitamin D-binding protein (DBP) is believed to form part of a scavenging system in the plasma for removing actin released from damaged cells. In the study presented here, we describe the crystal structure of the complex between actin and human vitamin D-binding protein at 2.5 A resolution. The complex contains one molecule of each protein bound together by extensive ionic, polar, and hydrophobic interactions. It includes an ATP and a calcium ion bound to actin, but no evidence of vitamin D metabolites bound to the DBP. Both actin and DBP are multidomain molecules, two major domains in actin and three in DBP. All of these domains contribute to the interaction between the molecules. DBP enfolds the end of the actin molecule, principally in actin subdomain 3 but with additional interactions in actin subdomain 1. This orientation is similar to the binding of profilin to actin, as predicted from previous studies. The more extensive interactions of DBP give an affinity for actin some 3 orders of magnitude higher than that for profilin. The larger "footprint" of DBP on actin also leads to an overlap with the actin-binding site of gelsolin domain I.

Actins↗
PubMed1989

Associations of blood pressure with self-report measures of anger and hostility among black and white men and women.

This study examined associations between blood pressure (BP) and dispositional variables pertaining to anger and hostility. Black and White 25- to 44-year old male and female normotensives and unmedicated mild to moderate hypertensives completed four reliable self-report scales--the Cook-Medley Hostility (Ho) Scale, the Trait Anger subscale of the State-Trait Anger Scale (STAS-T), and the Cognitive Anger and Somatic Anger subscales of the Cognitive-Somatic Anger Scale--plus the Framingham Anger Scale and the Harburg Anger Scale. They also engaged in three laboratory tasks--Type A Structured Interview (SI), a video game, and a cold pressor task--that elicit cardiovascular reactivity. Ambulatory BP readings at home and at work were also obtained from most subjects. Blacks had significantly higher Ho and lower STAS-T scores than did Whites. Women reported higher levels of somatic anger than did men. White women showed significant positive correlations between STAS-T and systolic BP (SBP) and diastolic BP (DBP) both at rest in the laboratory and during the SI. Black women revealed significant positive relationships between STAS-T and SBP and DBP at rest in the laboratory and at work as well as with DBP during the cold pressor test. For Black men, cognitive anger and DBP at rest were positively related. In contrast, White men revealed significant negative correlations between Ho scores and SBP at rest and during the video game; these men also showed significant negative relationships between somatic anger and SBP and DBP reactivity during the cold pressor test. Women, but not men, showed significant positive relationships between all four anger measures and ambulatory BP at work. Whereas main effects relating anger and cardiovascular measures were not apparent as a function of race, Blacks demonstrated significantly greater SBP and DBP reactivity than Whites during the cold pressor test, with the converse occurring during the SI. Men demonstrated significantly greater DBP reactivity than women during the video game. The present findings indicate that self-reports on anger/hostility measures and cardiovascular responses to behavioral tasks differ as a function of race but that relationships between anger and BP regulation need to take into account possible race-sex interactions and selection of anger/hostility measures.

Adult↗
PubMed1997

Low diastolic blood pressure, hypoalbuminemia, and risk of death in a cohort of chronic hemodialysis patients.

In a previous report, we showed that nutritional status and especially serum albumin had great predictive value for death in chronic hemodialysis patients, whereas blood pressure did not. In the present study, we analyzed the causes of death in consideration of the relationship between serum albumin and blood pressure. A total of 1,243 Okinawan patients (719 males, 524 females) undergoing hemodialysis in January 1991 were followed up through the end of 1995. Three hundred forty-two of the patients died, 45 received transplants, and 12 were transferred by the end of the follow-up period. The total duration of observation was 5,110.3 patient-years. Blood pressure as well as clinical and laboratory variables were determined immediately prior to the first dialysis session in January 1991. The crude death rate was 40.0% when the diastolic blood pressure (DBP) <70 mm Hg, 35.0% at 70 to 79 mm Hg, 25.0% at 80 to 89 mm Hg, 25.0% at 90 to 99 mm Hg, and 13.0% at >100 mm Hg. The death rate showed an inverse correlation with DBP. DBP showed a significant positive correlation with serum albumin (r = 0.137, P < 0.001) and age (r = -0.325, P < 0.0001). The adjusted odds ratio (95% confidence interval) of death was 0.84 (0.71 to 0.99) with 10 mm Hg increments in DBP when the reference DBP was less than 69 mm Hg. Low DBP may be a manifestation of malnutrition and/or cardiovascular disease in chronic hemodialysis patients. Target DBP levels may be higher levels in chronic hemodialysis patients than the general population.

Blood Pressure↗
PubMed1998

Ambulatory blood pressure monitoring and postprandial hypotension in elderly patients with isolated systolic hypertension. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

The present analysis was undertaken to evaluate postprandial (PP) changes in blood pressure (BP) assessed with ambulatory BP monitoring (ABPM) in elderly subjects with isolated systolic hypertension (ISH) on conventional measurement. A total of 530 patients (335 women and 195 men, aged 60-100 years, median 70 years) who performed an ABPM during the placebo run-in period of the Syst-Eur trial were included into the analysis. The PP changes in BP and heart rate (HR) were calculated by subtracting the mean systolic BP (SBP), diastolic BP (DBP) and HR in the 2 h preceding the main meal from the corresponding means covering the 2 h after the meal. The reproducibility of the postprandial fall in BP and heart rate (PPH) was assessed by contrasting the first and second ABPM in a subgroup of 147 patients who performed two ABPM's during the placebo run-in period. The mean SBP and DBP decreased and reached the nadir 2 h after the main meal while HR did not change. When PPH was assessed by comparing BP in the 2 h before and after the meal, both SBP and DBP decreased significantly (respectively -6.6 mm Hg, -5.4 mm Hg; P < 0.001). In 67.6% of all patients a decrease in SBP was observed and in 24.1% it exceeded 16 mm Hg. The corresponding values for DBP were 71.3% and 24.5% (DBP decreased more than 12 mm Hg). A greater fall in DBP was associated with a greater decrease in HR (r = 0.20, P < 0.001), while changes in SBP and HR were not interrelated. Regression analysis did not identify any significant covariate of PPH. Group means of PPH could be reproduced without significant changes in their values, but the within-subject reproducibility of the PP changes was low. There were no differences in PPH according to the place of residence of the patients. In conclusion, the descriptive analysis of the meal-induced changes in ABPM in elderly subjects with ISH showed that in every day circumstances most of them experience falls in both SBP and DBP within 2 h after the meal.

Aged↗
PubMed1999

A meta-analysis of randomised controlled trials (RCT) among healthy normotensive and essential hypertensive elderly patients to determine the effect of high salt (NaCl) diet of blood pressure.

To examine the effect of chronic NaCl ingestion on blood pressure (BP) in the elderly, a meta-analysis was undertaken of 11 randomised controlled trials of which five included patients > or =60 years of age only and six included patients with a mean age close to 60 years. The following databases were used: Medline, Embase, Current Contents, The Cochrane Library, the AMI and IPA databases. Mean erect systolic and diastolic blood pressures (SBP/DBP) on chronic (> or =9 weeks) high and low NaCl diets were recorded, the pooled mean effect, the pooled standard error and 95% confidence intervals (Cl) were calculated and linear regression was used to evaluate the potential association between NaCl intake and BP. When all trials were pooled, a chronic high NaCl diet significantly increased mean SBP and DBP by 5.58 mm Hg (95%Cl 4.31-6.85) and 3.5 mm Hg (95%Cl 2.62-4.38) respectively. There was a significant association between the level of NaCl intake and SBP (P = 0.05, r2 = 0.37) but not DBP (P = 0.76, r2 = 0.01). When trials were pooled separately, a chronic high NaCl diet increased SBP by 5.46 mm Hg (95%Cl 3.56-7.36) and DBP by 2.63 mm Hg (95%Cl 1.18-4.08) in trials including patients > or =60 years of age only, and increased SBP by 3.27 mm Hg (95%Cl 1.23-5.31) and DBP by 2.69 mm Hg (95%Cl 1.44-3.94) in trials including patients with a mean age close to 60 years. These data suggest that a chronic high NaCl diet in elderly patients with essential hypertension is associated with an increase in SBP and DBP, the association is significant for both SBP and DBP but more marked for SBP than DBP, the effect is more pronounced the older the patient and NaCl dose strongly predicts SBP in older patients.

Aged↗
PubMed2001

The effect of a change in ambient temperature on blood pressure in normotensives.

The aim of this study was to investigate the influence of ambient temperature on blood pressure (BP). BP measurements were taken in 20 normotensive volunteers who stayed in Greenland for a 6-week period. Measurements of systolic (SBP), diastolic (DBP) and heart rate (HR) were taken before (3 sessions), during (7-8 sessions) and after the journey (3 sessions). Each session consisted of five BP measurements in the supine position after at least 5 min rest. All five readings were averaged. Temperature data (mean +/- s.d.), collected from meteorological services, before, during and after Greenland were 15.7 +/- 0.6, 0.5 +/- 1.5 and 8.2 +/- 0.8 degrees C. SBP values were 116 +/- 7.0, 122 +/- 7.6 and 116 +/- 7.4 and DBP 63 +/- 5.2, 66 +/- 5.8 and 65 +/- 6.5 mm Hg, respectively. HR amounted to 58 +/- 7.4, 61 +/- 6.7 and 60 +/- 7.4 bpm. Significant differences existed between, before and during for SBP and DBP and between, during and after for SBP. Readings were grouped in four categories based on the temperature at the time of reading. For SBP as well as DBP a clear dose-response relationship was demonstrated between low temperature and high BP, although for DBP only a few correlations were statistically significant. Mean correlation coefficients for SBP and DBP against temperature were -0.44 (P < 0.001) and -0.27 (P < 0.005), respectively. our results are in favour of a moderate, but both significant and relevant increase in sbp and dbp when moving from higher to lower ambient temperature.

Adult↗
PubMed2006

Influence of childhood socioeconomic circumstances, height, and obesity on pulse pressure and systolic and diastolic blood pressure in older people.

This study assesses the association of childhood socioeconomic circumstances, height, and obesity with components of blood pressure. We selected 4009 people representative of the Spanish population aged 60 years and older, and estimated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) according to childhood social class, height, and obesity. No association was found between childhood social class and blood pressure. SBP showed an inverse gradient and DBP a direct gradient with height, although an independent association between height and DBP was found only in women. Stature was independently associated with increased DBP in women with central obesity, but there was no association between height and DBP in women without central obesity. Short stature was independently associated with increased PP. Body mass index and waist-to-hip ratio were independently associated with increased DBP in women, and waist-to-hip ratio was independently associated with increased PP in men, while waist circumference was independently associated with increased DBP and increased PP in women. These results do not support the assumed effect of socioeconomic circumstances in early life on blood pressure, which may depend on the context and/or study population. The relations observed between height and blood pressure support the hypothesis that PP could be a mediator of the association between short stature and increased cardiovascular risk. The relationship between obesity measures and components of blood pressure reinforces the recommendation to reduce body weight in order to reduce blood pressure.

Adult↗
PubMed2002

Can blood pressure responses to tests unmask future blood pressure trends and the need for antihypertensive medication? Ten years of follow-up.

An exaggerated blood pressure (BP) response to test may unmask the subjects who have a high risk of developing hypertension. In this prospective 10 years of follow-up, we examined whether the predictive value of casual BP measurements on future BP level and need for antihypertensive medication could be improved by using BP responses to different physical tests. At baseline, BP was recorded by casual measurements and intra-arterial monitoring. During the intra-arterial BP recording, standardized postural and exercise tests were performed on 97 healthy, untreated men (34 normotensive, 29 borderline hypertensive, and 34 mild hypertensive). After 10 years of follow-up, 87 of them (90%) returned for casual and non-invasive 24-h BP measurements. At follow-up, 20 (23%) of the men had antihypertensive medication. The prediction of casual systolic blood pressure (SBP) was best improved by SBP at 10 min after the dynamic exercise test (adj. R2 = 0.448; adj. R2 = 0.356 for casual SBP alone). The prediction of casual diastolic blood pressure (DBP) was most improved by DBP at 10 min after the dynamic exercise test (adj. R2 = 0.282; adj. R = 0.259 for casual BP alone). SBP in the supine test best improved the prediction of 24-h SBP (adj. R2 = 0 448; adj. R2 = 0.275 for casual SBP alone). DBP in the standing test best improved the prediction of 24-h DBP (adj. R2 = 0.252; adj. R2 = 0.214 for casual DBP alone). Pre-exercise DBP and casual SBP were the best predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.256; Cox-Snell R2 = 0.164 for casual SBP alone). In conclusion the prediction of future BP and need for antihypertensive medication can be improved by using BP measurements during postural and exercise tests. Future SBP is more predictable than DBP.

Adult↗
PubMed2002

A comparative study of osseointegration of Avana implants in a demineralized freeze-dried bone alone or with platelet-rich plasma.

PURPOSE: The purpose of this study was to assess the efficacy of demineralized bone powder (DBP) alone or combined in a mixture with platelet-rich plasma (PRP) used to enhance osseointegration of dental implants in a dog model. MATERIALS AND METHODS: Tissue integration was assessed using standard histomorphometric methods at 6 and 12 weeks after surgery. A total of 30 Avana dental implants (SooMin Synthesis Dental Materials Co, Busan, Korea) were inserted in the animals. They were self-tapping screw implants, 10 mm in length and 4 mm in diameter, made of commercially pure titanium. A titanium implant was then placed centrally in each defect. In each dog, the defects were treated with 1 of the following 3 treatment modalities:1) no treatment (control), 2) grafting with DBP, or 3) grafting with DBP and PRP. RESULTS: Histologic analysis showed that all of the bone defects surrounding the implants that were treated with DBP, with and without PRP, were filled with new bone. The defects that were not treated (control) showed new bone formation only in the inferior threaded portion of the implants. Histomorphometric results revealed a higher percentage of bone contact with DBP and PRP compared with control and DBP. CONCLUSION: These results suggested that bone defects around titanium implants can be treated successfully with DBP and that PRP may improve bone formation.

Analysis of Variance↗
PubMed2005

Developmental changes of bile acid composition and conjugation in L- and D-bifunctional protein single and double knockout mice.

Peroxisomal beta-oxidation is an essential step in bile acid synthesis, since it is required for shortening of C27-bile acid intermediates to produce mature C24-bile acids. D-Bifunctional protein (DBP) is responsible for the second and third step of this beta-oxidation process. However, both patients and mice with a DBP deficiency still produce C24-bile acids, although C27-intermediates accumulate. An alternative pathway for bile acid biosynthesis involving the peroxisomal L-bifunctional protein (LBP) has been proposed. We investigated the role of LBP and DBP in bile acid synthesis by analyzing bile acids in bile, liver, and plasma from LBP, DBP, and LBP:DBP double knock-out mice. Bile acid biosynthesis, estimated by the ratio of C27/C24-bile acids, was more severely affected in double knock-out mice as compared with DBP-/- mice but was normal in LBP-/- mice. Unexpectedly, trihydroxycholestanoyl-CoA oxidase was inactive in double knock-out mice due to a peroxisomal import defect, preventing us from drawing any firm conclusion about the potential role of LBP in an alternative bile acid biosynthesis pathway. Interestingly, the immature C27-bile acids in DBP and double knock-out mice remained unconjugated in juvenile mice, whereas they occurred as taurine conjugates after weaning, probably contributing to the minimal weight gain of the mice during the lactation period. This correlated with a marked induction of bile acyl-CoA:amino acid N-acyltransferase expression and enzyme activity between postnatal days 10 and 21, whereas the bile acyl-CoA synthetases increased gradually with age. The nuclear receptors hepatocyte nuclear factor-4alpha, farnesoid X receptor, and peroxisome proliferator receptor alpha did not appear to be involved in the up-regulation of the transferase.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Identification of glutathione conjugates and mercapturic acids of 1,2-dibromopropane in female BALB/c mice by liquid chromatography-electrospray ionization tandem mass spectrometry.

Based on recent results that 1,2-dibromopropane (1,2-DBP) causes hepatotoxicity and immunotoxicity in female BALB/c mice as well as a reduction of hepatic glutathione levels, the possible formation of glutathione conjugates and mercapturic acids of 1,2-DBP was investigated in vivo in the present studies. The following four metabolites were identified in the liver at 12 h after treatment with 1,2-DBP, by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS): M1, 2-hydroxypropylglutathione; M2, 2-oxopropylglutathione; M3, N-acetyl-S-(2-hydroxypropyl)-L-cysteine; and M4, N-acetyl-S-(2-oxopropyl)-L-cysteine. Ions of individual conjugates were observed at m/z 366, 364, 222 and 220, respectively. Characteristic product ions at m/z 237, 217, 204 and 202 for the identification of M1, M2, M3 and M4 were observed, respectively. In the sera isolated from the same animals, only mercapturic acids (M3 and M4) were observed by LC-ESI/MS. When female BALB/c mice were treated orally with 1,2-DBP at doses of 150, 300 and 600 mg kg(-1) once for 12 h, the production of glutathione conjugates and mercapturic acids in liver was apparently dose dependent, as were the concentrations of them in sera. When the production of metabolites from 1,2-DBP was investigated in liver following oral treatment with 600 mg kg(-1) 1,2-DBP for 6, 12, 24 and 48 h, metabolite concentrations were greatest at the first time point (6 h). The results explain the authors' previous studies that oral treatment with 1,2-DBP reduces the hepatic content of glutathione.

Acetylcysteine↗
PubMedDate not supplied

Male reproductive tract lesions at 6, 12, and 18 months of age following in utero exposure to di(n-butyl) phthalate.

In utero exposure of male rats to the antiandrogen di(n-butyl) phthalate (DBP) leads to decreased anogenital distance (AGD) on postnatal day (PND) 1, increased areolae retention on PND 13, malformations in the male reproductive tract, and histologic testicular lesions including marked seminiferous epithelial degeneration and a low incidence of Leydig cell (LC) adenomas on PND 90. One objective of this study was to determine the incidence and persistence of decreased AGD, increased areolae retention, and LC adenomas in adult rats following in utero DBP exposure. A second objective was to determine whether AGD and areolae retention during the early postnatal period are associated with lesions in the male reproductive tract. Pregnant Crl:CD(SD)BR rats were gavaged with corn oil or DBP at 100 or 500 mg/kg/day, 10 dams per group. Three replicates of rats (n = 30 rats per replicate) were exposed from gestation day 12 to 21 and the male offspring allowed to mature to 6, 12, or 18 months of age. Gross malformations in the male reproductive tract and histologic lesions in the testes were similar to those previously described. However, testicular dysgenesis, a lesion of proliferating LCs and aberrant tubules that has not been previously described in DBP-exposed testes, was diagnosed. The incidence of this lesion was approximately 20% unilateral and 7-18% bilateral in the high-dose group and was similar among all ages examined, implicating a developmental alteration rather than an age-related change. AGD and areolae retention were found to be permanent changes following in utero exposure to 500 mg/kg/day of DBP. Decreased AGD was a sensitive predictor of lesions in the male reproductive tract, relatively small changes in AGD were associated with a significant incidence of male reproductive malformations. In utero DBP exposure induced proliferative developmental lesions, some of which would have been diagnosed as LC adenomas by the morphological criteria set forth by the Society of Toxicologic Pathology. However, these lesions were dissimilar to traditional LC adenomas as the LCs were poorly differentiated and the lesions contained aberrant seminiferous tubules. While the morphology and incidence of this DBP-induced testicular developmental lesion has been fully characterized by this study, the detailed pathogenesis warrants further investigation.

Adenoma↗
PubMed2004

Estimated exposure to phthalates in cosmetics and risk assessment.

Some phthalates such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) and their metabolites are suspected of producing teratogenic or endocrine-disrupting effects. To predict possible human exposure to phthalates in cosmetics, the levels of DEHP, diethyl phthalate (DEP), DBP, and butylbenzyl phthalate (BBP) were determined by high-performance liquid chromatography (HPLC) in 102 branded hair sprays, perfumes, deodorants, and nail polishes. DBP was detected in 19 of the 21 nail polishes and in 11 of the 42 perfumes, and DEP was detected in 24 of the 42 perfumes and 2 of the 8 deodorants. Median exposure levels to phthalates in cosmetics by dermal absorption were estimated to be 0.0006 g/kg body weight (bw)/d for DEHP, 0.6 g/kg bw/d for DEP, and 0.103 g/kg bw/d for DBP. Furthermore, if phthalates in cosmetics were assumed to be absorbed exclusively via 100% inhalation, the median daily exposure levels to phthalates in cosmetics were estimated to be 0.026 g/kg bw/d for DEHP, 81.471 g/kg bw/d for DEP, and 22.917 g/kg bw/d for DBP, which are far lower than the regulation levels set buy the Scientific Committee on Toxicity, Ecotoxicity, and the Environment (CSTEE) (37 g/kg bw/d, DEHP), Agency for Toxic Substances and Disease Registry (ATSDR) (7000 g/kg bw/d, DEP), and International Programme on Chemical Safety (IPCS) (66 g/kg bw/d, DBP), respectively. Based on these data, hazard indices (HI, daily exposure level/regulation level) were calculated to be 0.0007 for DEHP, 0.012 for DEP, and 0.347 for DBP. These data suggest that estimated exposure to-phthalates in the cosmetics mentioned are relatively small. However, total exposure levels from several sources may be greater and require further investigation.

Absorption↗